Melatonin is a highly conserved molecule that regulates day/night rhythms; it is associated with sleep improvement, reactive oxygen species (ROS) scavenging, anti‐aging effects, and seasonal and ...circadian rhythms and has been a hot topic of research for decades. Using single‐cell RNA sequencing, a recent study describes a single‐cell transcriptome atlas for the rat pineal gland. Based on a more comprehensive analysis of the retrieved data (Mays et al., PLoS One, 2018, 13, e0205883), results from the current study unveiled the underappreciated gene regulatory network behind different cell populations in the pineal gland. More importantly, our study here characterized, for the first time, the day/night activation of autophagy flux in the rat pineal gland, indicating a potential role of autophagy in regulating melatonin synthesis in the rat pineal gland. These findings emphasized a hypothetical role of day/night autophagy in linking the biological clock with melatonin synthesis. Furthermore, ultrastructure analysis of pinealocytes provided fascinating insights into differences in their intracellular structure between daytime and nighttime. In addition, we also provide a preliminary description of cell‐cell communication in the rat pineal gland. In summary, the current study unveils the day/night regulation of autophagy in the rat pineal gland, raising a potential role of autophagy in day/night‐regulated melatonin synthesis.
Behavioral rhythms are a key aspect of species fitness, since optimize ecological activities of animals in response to a constantly changing environment. Cabled observatories enable researchers to ...collect long-term biological and environmental data in real-time, providing relevant information on coastal fishes’ ecological niches and their temporal regulation (i.e., phenology). In this framework, the platform OBSEA (an EMSO Testing-Site in the NW coastal Mediterranean) was used to monitor the 24-h and seasonal occurrence of an ecologically iconic (i.e., top-predator) coastal fish species, the common dentex (
Dentex dentex
). By coupling image acquisition with oceanographic and meteorological data collection at a high-frequency (30 min), we compiled 8-years’ time-series of fish counts, showing daytime peaks by waveform analysis. Peaks of occurrence followed the photophase limits as an indication of photoperiodic regulation of behavior. At the same time, we evidenced a seasonal trend of counts variations under the form of significant major and minor increases in August and May, respectively. A progressive multiannual trend of counts increase was also evidenced in agreement with the NW Mediterranean expansion of the species. In GLM and GAM modeling, counts not only showed significant correlation with solar irradiance but also with water temperature and wind speed, providing hints on the species reaction to projected climate change scenarios. Grouping behavior was reported mostly at daytime. Results were discussed assuming a possible link between count patterns and behavioral activity, which may influence video observations at different temporal scales.
Seasonal variations in daytime pineal 5-methoxytryptophol (5-ML) and in the daily pattern of both pineal 5-ML and melatonin concentrations were measured by radioimmunoassay in male and female ...jerboas, Jaculus orientalis. Pineal 5-ML content was found to be low in winter and spring and showed a short but marked increase in summer. A clear daily rhythm was present in pineal 5-ML in September, with high concentrations during daytime and low concentrations during nighttime. In May there was a considerable drop in the daytime values and a marked decrease in the amplitude of the rhythm, while in December the daily rhythm completely disappeared. On the contrary, a clear daily rhythm was observed for pineal melatonin in September, December, and May with high values during nighttime and low values during daytime; no differences in the amplitude of the rhythm could be observed. Illumination during early night prevented both the nocturnal decrease of 5-ML and the increase of melatonin in September; in May illumination had no clear effect on 5-ML, while it prevented the normal increase of melatonin. These results suggest a possible desynchronization between the regulation of 5-ML and melatonin synthesis and release, and stress the complexity of the mechanisms involved in the environmental synchronization of seasonal functions.
An exposure for 30 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced warm water swim stress-induced opioid analgesia in CF-1 male mice. Pre-treatment with naloxone (1.0 mg/kg) ...had comparable inhibitory effects on warm water swim induced analgesia. The magnetic stimuli also eliminated the day-night rhythm in stress-induced analgesia, with maximum inhibitory effects occurring in the dark period when peak analgesia was present. These results indicate that magnetic stimuli can significantly alter day-night rhythms of stress-induced activation of endogenous opioid systems and their behavioral and physiological consequences. These elevated night time effects may involve actions on the pineal gland, while the day time actions may involve alterations in the distribution and transport of Ca++ and or other divalent ions.
Despite the acknowledged impact of circadian rhythms on various aspects of life, behavioural tests with laboratory animals often overlook alignment with their natural activity patterns. This study ...aims to evaluate the influence of circadian variations on the results, validity, and reliability of different behavioural tests in rats.
Three behavioural tests, the Light-Dark Box Test (LDB), assessing anxiety-related behaviour and locomotor activity; the Buried Pellet Test (BPT), revealing olfactory abilities and motivation issues; and the Sucrose Preference Test (SPT), studying the anhedonic response, were employed to encompass multiple daytime-dependent behavioural aspects in male Sprague-Dawley rats.
Our findings underscore distinct circadian effects on locomotor activity, exploratory behaviour, olfactory acuity, motivation, and hedonic response. Notably, anxious behaviour remained unaffected by daytime conditions. Furthermore, decreased data variance was found to be correlated with conducting behavioural tests during the subjects’ active phase.
This study demonstrates extensive circadian influences on nearly all parameters investigated, coupled with a significant reduction in data variability during the active phase. Emphasising the importance of aligning experimental timing with rats’ natural activity patterns, our results suggest that conducting tests during the active phase of the animals not only refines test sensitivity , reduces stress, and provides more representative data, but also contributes to ethical animal research (3 R) and improves test relevance. This, in turn, enhances the reliability and validity of experimental outcomes in behavioural research and promotes animal welfare.
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•Circadian rhythms are often overlooked in behavioural studies on rodents.•Selected behavioural tests (LDB, BPT, SPT) cover diverse behavioural domains.•Significant diurnal influences on locomotion, exploration, olfaction, hedonism.•Enhanced test sensitivity and promoted animal welfare in active period.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•There is a day/night pattern of spontaneous activity in the DMH.•Sensitivity express a day/night pattern to ghrelin application in the DMH.•This rhythm is disrupted by the short term HFD ...consumption.•Prolonged HFD consumption deepens the disruption in the DMH network.
Dorsomedial hypothalamus (DMH) is a part of the feeding center involved in food intake and regulation of the metabolism. DMH neurons express many receptors for different metabolic cues which can modulate its network and influence animals’ behaviour. One of the metabolic peptides deliveredto this structure is ghrelin, the only well-known hunger signal, produced mainly in the stomach. Diet-induced obesity is a physiological model of obesity widely used in research. Here we investigated how time-of-day and high-fat diet (HFD) affect neuronal networks and the sensitivity to the metabolic information received by the DMH. Our results indicate that even a short period of HFD (2–3 weeks) consumption can cause dysregulation of the DMH neuronal network, manifested as a disruption of the day/night pattern of basal activity and altered sensitivity to incoming information. We showed for the first time a day/night pattern of sensitivity to ghrelin in the DMH, with a higher level during the behaviorally active phase of animals. This day/night rhythm of sensitivity to ghrelin was reversed in HFD group, causing a stronger effect during the non-active phase. After prolongation of the HFD consumption to 7–8 weeks we observed an increase in the responsiveness to ghrelin, than during the short-term diet.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mitochondrial network dynamics may play role in metabolic homeostasis. Whether mitochondrial network dynamics are involved in adaptations to day–night fluctuations in energy supply and demand is ...unclear. Here we visualized and quantified the mitochondrial network morphology in human skeletal muscle of young healthy lean and older individuals with obesity over the course of 24 h
Muscle biopsies taken at 5 timepoints over a 24-hour period obtained from young healthy lean and older metabolically impaired obese males were analyzed for mitochondrial network integrity with confocal laser scanning microscopy. Variation of level of fragmentation over the course of the day were aligned with variation of mitochondrial respiration over the day
Young healthy lean individuals displayed a day–night rhythmicity in mitochondrial network morphology, which aligned with the day–night rhythmicity of mitochondrial respiratory capacity, with a more fused network coinciding with higher mitochondrial respiratory capacity. In the older individuals with obesity, the mitochondrial network was more fragmented overall compared to young healthy lean individuals and completely lacked 24 h rhythmicity, which was also true for the mitochondrial respiratory capacity
Our data shows a paralleled rhythmicity between mitochondrial network morphology and mitochondrial oxidative capacity, which oscillates over the course of a mimicked real-life day in human skeletal muscle of young, healthy lean individuals. In older individuals with obesity, the lack of a 24-hour rhythmicity in mitochondrial network connectivity was also aligned with a lack in respiratory capacity. This suggests that 24-hour rhythmicity in mitochondrial network connectivity is a determinant of rhythmicity in mitochondrial respiratory capacity. Thus, restoring mitochondrial network integrity may promote mitochondrial respiratory capacity and hence contribute to blunting the metabolic aberrations in individuals with a disturbed 24-hour rhythmicity in metabolism, like older individuals with obesity.
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•Myocellular mitochondrial network integrity in healthy young lean males is rhythmic.•In young healthy males mitochondrial network and respiration align.•Mitochondrial network integrity is not rhythmic in older metabolic impaired males.•In older obese males mitochondrial network and respiration are not rhythmic.•MFI provides quantitative information on mitochondrial network connectivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Insulin Growth Factor Binding Protein 4 (IGFBP-4), Stanniocalcin-2 (STC-2) and Pregnancy-Associated Plasma Protein-A (PAPP-A) have a well-documented involvement in several physiological functions in ...humans but predictors of their circulating levels remain largely unknown. We aimed to identify anthropometric and biochemical parameters associated with circulating levels of IGFBP-4/STC-2/PAPP-A axis (ISPa) cross-sectionally and to study their day-night variation and their regulation in response to mixed meal and exercise.
One hundred twenty two healthy individuals were evaluated cross-sectionally. Subgroups were subjected to standardized mixed meal ingestion in increasing quantities of 125mL or 250mL, or aerobic exercise for 30min, or day-night rhythm study. Main outcome measurements were circulating IGFBP-4 (total and intact), STC-2 and PAPP-A levels.
In multivariate models, the main predictors of serum total IGFBP-4 were PAPP-A and female gender. Intact IGFBP-4 was positively associated with serum creatinine. Height was inversely and female gender and % of total body fat were positively correlated with STC-2. PAPP-A decreased after ingesting both the 125mL (p=0.03) and 250mL quantities (p=0.001), while total IGFBP-4 was reduced after the 250mL quantity (p=0.001). Exercise increased STC-2 and PAPP-A levels (p<0.001 for both). Intact, and to a lesser extent total, IGFBP-4 displayed a cortisol-like day/night variation.
We report for the first time anthropometric and physiological modulators of ISPa serum levels in healthy humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Skeletal muscle mitochondrial function and energy metabolism displays day-night rhythmicity in healthy, young individuals. Twenty-four-hour rhythmicity of metabolism has been implicated in the ...etiology of age-related metabolic disorders. Whether day-night rhythmicity in skeletal muscle mitochondrial function and energy metabolism is altered in older, metabolically comprised humans remains unknown.
Twelve male overweight volunteers with impaired glucose tolerance and insulin sensitivity stayed in a metabolic research unit for 2 days under free living conditions with regular meals. Indirect calorimetry was performed at 5 time points (8 AM, 1 PM, 6 PM, 11 PM, 4 AM), followed by a muscle biopsy. Mitochondrial oxidative capacity was measured in permeabilized muscle fibers using high-resolution respirometry.
Mitochondrial oxidative capacity did not display rhythmicity. The expression of circadian core clock genes BMAL1 and REV-ERBα showed a clear day-night rhythm (p < 0.001), peaking at the end of the waking period. Remarkably, the repressor clock gene PER2 did not show rhythmicity, whereas PER1 and PER3 were strongly rhythmic (p < 0.001). On the whole-body level, resting energy expenditure was highest in the late evening (p < 0.001). Respiratory exchange ratio did not decrease during the night, indicating metabolic inflexibility.
Mitochondrial oxidative capacity does not show a day-night rhythm in older, overweight participants with impaired glucose tolerance and insulin sensitivity. In addition, gene expression of PER2 in skeletal muscle indicates that rhythmicity of the negative feedback loop of the molecular clock is disturbed.
NCT03733743.
•Diurnal rhythmicity of mitochondrial function is attenuated in older and metabolically compromised men.•Rhythmicity of the biological clock gene PER2 is disturbed in skeletal muscle of these volunteers.•Metabolic flexibility in 24-h metabolism is diminished, with a lack of a typical feeding-fasting cycle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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